CHANGING PARDIGMS IN BREAST SURGERY Dr S Sahni Senior Consultant Breast Surgeon Indraprastha Apollo Hospital

New Paradigms From To Anatomical concept of cancer spread Aggressive radio-surgery To Biological concept of cancer spread Targeted conservative treatments Dr S.R.Sahni,2008

MASTECTOMY vs CONSERVATION

INDICATIONS FOR MASTECTOMY Inability to obtain radiation therapy Multicentricity Multifocality Large operable cancers , unfit for radiation ?BRCAness Skin involvement

ARE THESE ABSOLUTE OR OBSELETE?………

DEFINITIONS Multicentricity- Two or more foci of cancer in different quadrants of the same breast Multifocality- two or more foci of cancer in the same breast quadrant

T Margin positivity is conditioned by the extent of breast resection. 57% 40% 16% CASES T 1 2 3 CM. >40% of specimen showed invasive foci at >2cm from the primary Holland 1985

TRADITIONAL PARADIGM Multicentric (MC) & Multifocal(MF) Breast Cancer are regularly considered a relative contraindication for Breast Conserving Therapy (BCT)

THE REASONING Perceived higher risk for in-breast recurrence since it is assumed that in MF/MC cancer the risk of more invasive foci in the breast is greater and radiotherapy less effective Bad cosmetic results –wider excisions/ multiple wide excisions and larger boost volumes with more fibrosis

MRI The use of MRI is associated with increased Mastectomy rates. Most Likely due to extra findings: considered to be MC or MF disease Houssami N, Morrow M et al Pre-operative magnetic resonance imaging in breast cancer:meta analysis of surgical outcomes. Ann Surg. 2013

THE EVIDENCE ? Is MF/MC disease associated with worse disease free and overall survival? Is BCT in MF/MC disease associated with higher local relapse rates?

Multicentric (MC) & Multifocal(MF) Breast Cancer are regularly considered a relative contraindication for Breast Conserving Therapy (BCT)

Vera-Badillo et al Effect of multifocality and multicentricity on outcome in early stage breast cancer. BCRT. 2014 N= 67,557 22 studies 9.5% MF/MC

MF/MC versus unifocal Multifocal/ Multicentric (%) Unifocal P N patients 6,565 62,326 Premenopausal 15 5.3 0.003 Postmenopausal 23 12 unknown 62 82 Histology Ductal 55 0.006 Lobular 8.5 0.2 Mixed 0.5 4.1 OTHER 36 41 Tumour size T1 29 31 <0.001 T2 16 17 T3 28 1.9 T4 0.3 Unknown 27 50 MF/MC versus unifocal Vera-Badillo et al Effect of multifocality and multicentricity on outcome in early stage breast cancer. BCRT. 2014

MF/MC versus unifocal Vera-Badillo et al Effect of multifocality and multicentricity on outcome in early stage breast cancer. BCRT. 2014 Treatment modality Multifocal/ Multicentric (%) Unifocal P Breast Conserving Surgery 26 54 <0.001 Chemotherapy 20 Radiotherapy 11 6.9 Hormone therapy 30 27

MF/MC versus unifocal Conclusion “Multifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Further validation of the independent prognostic impact of multifocality is warranted” Vera-Badillo et al Effect of multifocality and multicentricity on outcome in early stage breast cancer. BCRT. 2014

Netherlands Cancer Institute (NKI-AVL) 1980-2008 BCT RADIOTHERAPY (RT) IN THE NKI-AVL

Increased use of adjuvant systemic therapy NKI –AVL, 1988-2008 1980-1987 1988-1998 1999-2008 SYSTEMIC THERAPY 203 (19%) 1479 (41%) 1959 (51%) HORMONAL 35 (3%) 1031 (28%) 1510 (40%) CHEMOTHERAPY 172 (16%) 557 (15%) 1138 (30%) Node-negative patienys 11 (6%) 292 (22%) 615 (36%)

Netherlands Cancer Institute (NKI-AVL) 417 patients with local recurrence (LR) 5 yrs LR-rate: 2% 10 yrs LR-rate: 5%

Data now online: Ann Surg Oncol – 2/2015 – open access The Breast (in press) mahdi@rezai.org European Breast Center Duesseldorf Luisen hospital /Germany

tumor size histopathology grading intrinsic subtype Oncoplastic Study (Rezai M- Kern P), n= 1035, 2004-2009, (follow-up: 5,2 years) Analysis of recurrence according to ... tumor size histopathology grading intrinsic subtype age surgical technique European Breast Center Duesseldorf Luisen hospital /Germany

tumor location surgical technique resection volume age Oncoplastic Study (Rezai, Kern), n= 1035, 2004-2009, (follow-up: 5,2 years) Analysis of aesthetic result and pat.satisfaction according to tumor location surgical technique resection volume age BMI mahdi@rezai.org European Breast Center Duesseldorf Luisen hospital /Germany

Cohort: n= 1035 patients, eligible for analysis: n= 944 patients Age at diagnosis (average): 57.6 years (median 58 years) Rezai M- Kern P- Annals Surgical of oncology 2015

Outcome (Recurrence) in the cohort Out of 944 patients, 38 experienced a recurrence  5-years-recurrence rate 4,0% recurrence rate in correlation with the age at time of surgery: < 40 years: 8,3% 40-49 years: 4,8% 50-59 years: 3,1% 60-69 years: 3,9% > 70 years: 3,6% Rezai M- Kern P- Annals Surgical of oncology 2015

Recurrence rate – correlated with histopathology Non-invasive lesions had the highest recurrence rate  DCIS: 6,7% Ductal invasive and lobular histology did not differ in recurrence rate  invasiv-duktal: 3,5%  invasiv-lobulär: 3,6% no difference in outcome – ductal or lobular histology! Rezai M- Kern P- Annals Surgical of oncology 2015

Margin status and re-excision-rate   11.4% (108/944) with unclear margins at 1st surgery 10.2% (11/108) of patients did not undergo a re-excision. No recurrence were seen in these patients at 5,2 years.   . Rezai M- Kern P- Annals Surgical of oncology 2015

Oncoplastic techniques European Breast Center Duesseldorf Luisen hospital /Germany 28 Brustzentrum Düsseldorf Luisenkrankenhaus– Rezai M/Kellersmann S/Knispel S/Kern P

Oncoplastic Surgery Combining lumpectomy or quadrantectomy with local or regional tissue rearrangement so that the breast should be conserved and reshaped to avoid significant deformity

Five major principles of Oncoplastic techniques GLANDULAR ROTATION DERMO GLANDULAR ROTATION TUMOR ADAPTED REDUCTION MAMMOPLASTY BCT – THORACO EPIGASTRIC FLAP (TEF) BCT – ADVANCEMENT FLAP Rezai M, Veronesi U. Oncoplastic principles in breast surgery. Breast Care 2007;2:277-278 Rezai M- Kern P- Annals Surgical of oncology 2015

mahdi@rezai.org European Breast Center Duesseldorf Luisen hospital /Germany

Glandular Rotation 63.8% © Rezai Rezai M, Veronesi U. Oncoplastic principles in breast surgery. Breast Care 2007;2:277-278

Quadrantectomy

Breast gland reconstruction

Tumor-adapted reduction mammoplasty 20.8% Modified inferior pedicle (M.Rezai) © Rezai Rezai M, Veronesi U. Oncoplastic principles in breast surgery. Breast Care 2007;2:277-278

BCT with advancement flap 4.4% (M.Rezai Rezai M, Veronesi U. Oncoplastic principles in breast surgery. Breast Care 2007;2:277-278

(Tumoradapted Rotation mastopexy 6.7% (M. Rezai) Rezai M, Veronesi U. Oncoplastic principles in breast surgery. Breast Care 2007;2:277-278

Dr S.R.Sahni,2007

Dr S.R.Sahni,2007

BCT Thoraco Epigastric Flap and others 3% © Rezai

5 years overall survival G1: 100% , G2: 95,1 % G3: 90,2 % Rezai M- Kern P- Annals Surgical of oncology 2015

% Overall survival according to intrinsic subtype Histopath. subtyp Number Number of event % Luminal A 592 34 558 94.3% Tripelnegt. 97 18 70 81.4% Lum.B Her2 Posit. 80 9 71 88.8% Lum.B Her2 negat 73 11 62 84.9% Her2 Posit. (non Lum) 54 8 46 85.2% Unknown 48 40 83.3% Total 944 88 856 90.7% mahdi@rezai.org

87 % were satisfied with the surgical outcome Patient reported outcome (PRO): surgical result 87 % were satisfied with the surgical outcome

Choice of oncoplastic technique and DFS Cumulative DFS p=0.166 years DFS did not correlate with the choice of a particular onco- plastic technique(p=0.166) 45 Brustzentrum Düsseldorf Luisenkrankenhaus– Rezai M/Kellersmann S/Knispel S/Kern P

Take HOME Beware of the MRI, use it sensibly MC/MF has worse prognosis: adjuvant systemic therapy Adjuvant systemic therapy reduces LR by half Whole breast RT reduces LR rates by another half

Take HOME Optimal imaging Consider neo-adjuvant chemo and radiation therapy Perform complete excision/s +/- oncoplasty

Surgery is only one sub-step out of multiple steps in breast cancer treatment. Thus, both a diagnostic and an oncological expertise are indispensable and a definite requirement.

ACKNOWLEDGEMENTS Prof Umberto Veronesi Prof Mahdi Rezai Prof Emile Rutgers

THANK YOU Dr S.Sahni Senior Consultant Breast Surgeon Indraprastha Apollo Hospital New Delhi